This is an initial submission for a K23 award by Dr. Meyeon Park at the University of California, San Francisco. Dr. Park is establishing herself as a young investigator in patient-oriented clinical research of chronic kidney disease (CKD). This K23 award will provide Dr. Park with the support necessary to accomplish the following goals: 1) to study the mechanisms of kidney injury and CKD onset in individuals with cardiovascular disease; 2) to study novel risk factor pathways in individuals with cardiovascular disease who develop CKD; and 3) to become an expert in the novel application of a method of magnetic resonance imaging for detecting kidney hypoxia in vivo. To achieve these goals, Dr. Park has assembled a mentoring team led by a primary mentor, Dr. Michael Shlipak, Professor and Chief of the Division of General Internal Medicine at the San Francisco VA Medical Center, and a co-mentor, Dr. Chi-yuan Hsu, Professor and Chief of the Division of Nephrology at UCSF. Her larger mentoring team also includes Dr. Eric Vittinghoff, Professor in the Division of Biostatistic at UCSF and an expert in longitudinal analyses of repeated measures. Dr. Peter Ganz, Dr. Yerem Yeghiazarians, and Dr. Zhen Jane Wang are close collaborators and scientific advisors who will lend scientific expertise in the areas of cardiovascular biomarkers, coronary angiography, and renal imaging, respectively. Cardiovascular disease (CVD) is extremely prevalent in the U.S. adult population and is a strong and independent risk factor for development of CKD, which adds excess morbidity and mortality to an already deadly condition. Few studies have focused on identifying risk factors for development of CKD in this group, and there is incomplete understanding of the mechanisms of early kidney disease onset in this setting. Dr. Park's research will first examine the impact of CVD on kidney injury detected by novel urine biomarkers and on clinically evident kidney disease outcomes (Aim 1). She will then focus on individuals with ischemic heart disease to examine candidate risk factor pathways leading from atherosclerosis to reduced kidney function in this group, including potentially via acute kidney injury (Aim 2). Finally, she will study kidney hypoxia using Blood Oxygen Level-Dependent magnetic resonance imaging (BOLD-MRI) and correlate this with kidney injury markers (Aim 3). This research will form the basis for future work investigating strategies for CKD risk stratification and early detection and intervention among CVD patients, which will be proposed in an R01 grant application before the end of the K award period.
Cardiovascular disease is a worldwide health problem and a major risk factor for kidney disease and death. The development of chronic kidney disease in a person with cardiovascular disease complicates management, reduces health status, and increases mortality risk substantially. As the mechanisms for the development of kidney disease in these individuals are not understood, we plan to investigate how cardiovascular disease leads to kidney disease.
